Sunburn and Cutaneous Squamous Cell Carcinoma

Importance: While UV radiation is a known carcinogen associated with cutaneous squamous cell carcinoma (cSCC), sunburn's specific role remains less clear. Objective: To quantitatively assess the association between sunburn history and the risk of developing cSCC. Data Sources: A comprehensive search of Embase, PubMed, and Cochrane Library (CENTRAL) was conducted from inception up to May 6, 2025, with no language or date restrictions. Search terms included Non melanoma skin cancer or nonmelanoma skin cancer or NMSC or squamous cell carcinoma or SCC or cSCC or Bowen disease and Sunburn or sun exposure or sunlight or sun damage or ultraviolet radiation or ultraviolet light or ultraviolet rays. Study Selection: The study included analytical investigations of the general population that assessed the association between cSCC and any type of sunburn history at any age. The initial screening of 9310 titles and abstracts by 3 masked independent reviewers resulted in 279 articles for full-text review, with 43 ultimately meeting eligibility criteria. Data Extraction and Synthesis: This study follows the Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guideline. Two reviewers worked independently to extract relevant data. The random effects DerSimonian-Laird method was used to pool data. Main Outcome and Measures: The main outcome was the risk of developing cSCC. Main measures included sunburn frequency (both undefined and painful, blistering, and/or severe) in any life period, categorized into ordinal variables: none, low, medium, and high. The primary analysis was the most adjusted measure of association, standardized to odds ratio (OR). This incorporated adjusted measures of association when available and unadjusted measures when adjusted measures were absent. Results: Seventeen studies with a combined 321 473 participants were included in the meta-analysis. Pooled analyses of the most adjusted results revealed significantly increased odds of developing cSCC with medium (OR, 1.51; 95% CI, 1.26-1.81) and high (OR, 1.69; 95% CI, 1.39-2.06) lifetime painful, blistering, and/or severe sunburn frequencies. Similarly, high frequencies of painful, blistering, and/or severe sunburns in childhood were significantly associated with increased cSCC odds (OR, 3.11; 95% CI, 1.26-7.66). A history of any painful, blistering, and/or severe sunburn was also significantly associated with increased odds of cSCC (OR, 1.38; 95% CI, 1.06-1.79). Conclusions and Relevance: This meta-analysis supports an association between painful, blistering, and/or severe sunburns and cSCC.